Hyperoxaluria is reduced and nephrocalcinosis prevented with an oxalate-degrading enzyme in mice with hyperoxaluria.

Abstract

BACKGROUND/AIMS:

Hyperoxaluria is a major risk factor for recurrent urolithiasis and nephrocalcinosis. We tested an oral therapy with a crystalline, cross-linked formulation of oxalate-decarboxylase (OxDc-CLEC) on the reduction of urinary oxalate and decrease in the severity of kidney injury in two models: AGT1 knockout mice (AGT1KO) in which hyperoxaluria is the result of an Agxt gene deficiency, and in AGT1KO mice challenged with ethylene glycol (EG).

METHODS:

Four different doses of OxDc-CLEC mixed with the food, or placebo were given to AGT1KO mice (200 mg/day, n = 7) for 16 days and to EG-AGT1KO mice (5, 25, and 80 mg, n = 11) for 32 days.

RESULTS:

Oral therapy with 200 mg OxDc-CLEC reduced both urinary (44%) and fecal oxalate (72%) in AGT1KO mice when compared to controls. Similarly, in EG-AGT1KO mice, each of the three doses of OxDc-CLEC produced a 30-50% reduction in hyperoxaluria. A sustained urinary oxalate reduction of 40% or more in the 80 mg group led to 100% animal survival and complete prevention of nephrocalcinosis and urolithiasis.

CONCLUSION:

These data suggest that oral therapy with OxDc-CLEC may reduce hyperoxaluria, prevent calcium oxalate nephrocalcinosis and urolithiasis, and can represent a realistic option for the treatment of human hyperoxaluria, independent of cause.

• Authors: Danica Grujic, Eduardo C Salido, Bhami C Shenoy, Craig B Langman, Margaret E McGrath, Reena J Patel, Aftab Rashid, Saraswathi Mandapati, Chu W Jung, Alexey L Margolin
• Journal: American journal of nephrology (Am J Nephrol) Vol. 29 Issue 2 Pg. 86-93 ( 2009) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 18698135 (Publication Type: Journal Article)
• Copyright: Copyright (c) 2008 S. Karger AG, Basel.

Chemical References

• Amino Acid Transport Systems
• Oxalates
• Slc7a13 protein, mouse
• Peptide Hydrolases
• Carboxy-Lyases
• oxalate decarboxylase
• Ethylene Glycol

Topics

• Administration, Oral
• Amino Acid Transport Systems (genetics)
• Animals
• Carboxy-Lyases (chemistry, pharmacokinetics, pharmacology)
• Chemistry, Pharmaceutical
• Crystallization
• Disease Models, Animal
• Ethylene Glycol (toxicity)
• Feces
• Hyperoxaluria (drug therapy, genetics, metabolism)
• Kidney (physiology)
• Male
• Mice
• Mice, Knockout
• Nephrocalcinosis (chemically induced, metabolism, prevention & control)
• Oxalates (urine)
• Peptide Hydrolases (metabolism)
• Urolithiasis (genetics, metabolism, prevention & control)